Despite concerted efforts at investigating and disseminating the health risks of tobacco dependence, millions of Americans continue to smoke chronically. Drug abusers have twice the smoking rate of the general population and suffer increasingly costly quality of life and health consequences. For example, more than 80% of opioid dependent individuals on buprenorphine maintenance therapy smoke cigarettes. Recent research suggests that cigarette smoking adversely affects brain morphology, blood flow, biochemistry, and cognition. These smoking-related brain abnormalities resemble those observed in chronic drug use and involve major components of the reward circuit, implicated in the initiation and maintenance of all forms of addiction. Tobacco dependence is also related to higher levels of non-nicotinic drug use after drug abuse treatment. The impact of combined opioid and tobacco dependence on neurobiology and behavior has not been evaluated systematically, and its relations to high smoking relapse rates in this population are poorly understood. Recent research implicates abnormalities in the reward circuitry as major contributor to relapse in all drug use, but corresponding evidence from opioid users in tobacco dependence treatment is lacking. The main purpose of this component is to a) obtain magnetic resonance-derived and neurocognitive measures of the integrity of frontal-subcortical brain circuits in opioid dependent individuals on buprenorphine replacement therapy before their extended, innovative tobacco dependence treatment, b) determine if these measures diffenentiate successful and unsuccessful quitters, and c) determine their ability to pnedlct \obacco dependence treatment response at 3, 6, 12, and 18 months after treatment randomization. Exploratory genetic studies will address the influence of select single nucleotide polymorphisms on the main neurobiological and treatment outcome measures and the impact of these polymorphisms on quit rates. The overarching purpose of this research is to enable - within the existing framework of the Center - the development of a unique collaboration among two productive research teams at UCSF that both have aimed for many years to help reduce the overall impact of drug abuse on society. This multidisciplinary component, performed as part of a larger clinical trial of extended and innovative tobacco dependence treatment, is expected to increase our understanding of the extent to which neurobiological and cognitive deficiencies as well as specific genotypes contribute to an individual's ability to maintain long-term tobacco abstinence.